FDA Committee Looks Unfavorably on Antidepressant Gepirone

It appears that even after four tries, the antidepressant gepirone will have a hard time winning approval from the FDA, following a Dec. 2 advisory committee.

After a day of testimony from FDA scientists and representatives from gerpirone's sponsor, Fabre-Kramer Pharmaceuticals, a majority the agency's Psychopharmacologic Drugs Advisory Commitee voted that the company did not demonstrate substantial evidence of effectiveness for the drug. The tally was nine against, and four in the affirmative.

Gepirone is classified as both an antidepressant and antianxiolytic of the azapirone class, and acts as a selective partial agonist of the 5-HT1A receptor, which binds the neurotransmitter serotonin. Fabre-Kramer touts that gepirone, which was initially developed by Bristol-Myers Squibb and subsequently outlicensed, has a unique mechanism of action.

One of the obstacles gepirone ran into before the committee meeting were a number of short-term trials in which gepirone failed to show any difference in effectiveness in effectiveness between the drug and a placebo. However, re-analyses conducted by the FDA found that the placebo was marginally more effective than gepirone.

The committee also voted 11-2 that Fabre-Kramer demonstrated the saferty of the gepirone. Despite the negative tone taken by some members at the meeting, company representatives said they remain optimistic the drug will win approval.

"Gepirone ER is a drug with a novel mechanism that promises to work for patients where other drugs don't," Stephen Stahl, MD, a psychiatry professor at the University of California San Diego School of Medicine, said in a company news release.

“There's more at stake here than just gepirone," he added. “The larger concern is that if the FDA does not approve this drug, it will discourage companies from trying to create new psychiatric drugs, which many companies already avoid because of the high failure rate.

“It could have a chilling effect on future development in this class.”